The ongoing objective of our research, since the establishment of the HFH MEG Lab, has been to develop hardware, software, and techniques to expand the utility of Magnetoencephalography (MEG), both as a clinical diagnostic tool, and as a modality for basic neuroscience studies. With the proliferation of MEG sys- tems both in the U.S. and worldwide, and the availability of CPT codes for some clinical MEG studies, the development of new and more effective clinical applications to enable users to more fully exploit these costly systems has become our highest priority. Accordingly we are developing new analytical tools and demon- strating that MEG data contains much more clinically useful information than can be found using only the usual dipole techniques. For example, the integration of our Multi Resolution FOCUSS with Principal Com- ponent Analysis (PCA) or Singular Value Decomposition (SVD) shows promise of enhanced computational efficiency and the ability to identify regions of high brain coherence indicative of epileptic tissue. During the proposed grant, these new techniques will be further developed and applied to neurologic and learning dis- orders. In Specific Aim One, interoperative source confirmation will be compared to results of our mapping techniques. DC-MEG will be used to monitor interictal cortical excitability in migraine patients and how this excitability responds to anti-migraine medications. Determination of focal secondary generalized epileptic activity may be used to predict successful surgical resections. In Specific Aim Two we propose to continue the development of new analytical tools and to make them available to the MEG community on the Internet as they become validated. In particular, we will add new functionality to our "MEG Tools" software suite by incorporating ICA, Frequency Analysis, and MEG co-registration with Diffusion Tensor Imaging (DTI). In Specific Aim Three, our new techniques will be applied to imaging differences in cortical activation between normal readers and individuals with learning disorders during reading tasks. These techniques will be used to map various cortical areas activated by auditory and visual lexical stimuli, and to differentiate the re- sponses of normal and reading disabled individuals. The exquisite temporal and spatial resolution of MEG, enhanced by these new imaging techniques, will provide clinicians and researchers new noninvasive meth- ods to investigate pathological and normal neurological functioning. [unreadable] [unreadable] [unreadable]